B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5.
Although most leukocytes, T lymphocytes in particular, respond to several different chemokines, there is virtually no information on chemokine activities and chemokine receptors in B lymphocytes. A putative chemokine receptor, BLR1, that is expressed in Burkitt's lymphoma cells and B lymphocytes was cloned a few years ago. Deletion of the gene for BLR1 yielded mice with abnormal primary follicles and germinal centers of the spleen and Peyer's patches, reflecting the inability of B lymphocytes to migrate into B cell areas. By screening expressed sequence tag DNA sequences, we have identified a CXC chemokine, termed B cell-attracting chemokine 1 (BCA-1), that is chemotactic for human B lymphocytes. BCA-1 cDNA encodes a protein of 109 amino acids with a leader sequence of 22 residues. The mature protein shares 23-34% identical amino acids with known CXC chemokines and is constitutively expressed in secondary lymphoid organs. BCA-1 was chemically synthesized and tested for activity on murine pre-B cells 300-19 transfected with BLR1 and on human blood B lymphocytes. In transfected cells, BCA-1 induced chemotaxis and Ca2+ mobilization demonstrating that it acts via BLR1. Under the same conditions, no activity was obtained with 10 CXC and 19 CC chemokines, lymphotactin, neurotactin/fractalkine and several other peptide ligands. BCA-1 was also a highly effective attractant for human blood B lymphocytes (which express BLR1), but was inactive on freshly isolated or IL-2-stimulated T lymphocytes, monocytes, and neutrophils. In agreement with the nomenclature rules for chemokine receptors, we propose the term CXCR5 for BLR1. Together with the observed disturbance of B cell colonization in BLR1/ CXCR5-deficient mice, the present results indicate that chemotactic recruitment by locally produced BCA-1 is important for the development of B cell areas of secondary lymphoid tissues.
Legler
D F
DF
Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland.
Loetscher
M
M
Roos
R S
RS
Clark-Lewis
I
I
Baggiolini
M
M
Moser
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000276:immunology*; D019743:Chemokines, CXC; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D008024:Ligands; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D019204:GTP-Binding Proteins